Work to date (HD 5572) has defined renal functional correlates of pregnancy in rats with normal gestation. In the current year experiments on Sprague Dawley rats will be concluded by measuring the intrarenal distribution of blood flow in gravid and non-pregnant rats using a labeled microsphere technique. In the remaining years renal hemodynamics and volume homeostasis will be investigated in animals with abnormal pregnancies. Objectives are: A. Measure renal function, intravascular and extracellular volume during pregnancy in (1) Wistar rats with spontaneous hypertension (SHR); (2) Animals with autologous immune complex disease affecting primarily the renal glomerulus; (3) Rats with chronic parenchymal kidney disease involving mainly the tubules. In each of these models blood pressure will be monitored prior to and during gestations. Clearances of inulin and its volume of distribution as well as PAH and its extraction and plasma volume will be measured in term gravid animals and simultaneously studied lettermate (SHR) or aged matched (renal disease) virgin controls. B. Evaluate the renal response to graded saline infusions in these 3 groups of rats with complicated gestation. Infusate volume will be calculated to expand animals by a volume equal to 10-20 percent of their anticipated inulin space, and filtered and excreted sodium will be measured during and for 2 hours after the infusion. C. Survey effects of salt and repeated pregnancies on the course of gestations and the natural history of these diseases. Experiments will be performed after 3 successive pregnancies, as well as in rats ingesting high and low sodium diets. D. Establish morphological correlations with the observed pathophysiology in these models. Autopsies will include light and electron microscopical examinations, most specifically of the kidney (e.g., interstitial medullary cells). Long term goals are to apply this information towards improving the management of human pregnancy complicated by hypertension or renal disease. BIBLIOGRAPHIC REFERENCES: Lindheimer, M.D., Katz, A.I.: Renal changes during pregnancy: Their relevance to volume homeostasis, in Physiological Adjustments to Pregnancy. Hytten, F., ed. Clin. in Ob. Gyn. 2:345, 1975.